title: Enhanced L1CAM expression on pancreatic tumor endothelium mediates selective tumor cell transmigration.
abstract: L1 cell adhesion molecule (L1CAM) is a transmembrane cell adhesion molecule initially defined as a promigratory molecule in the developing nervous system that appears to be also expressed in some endothelial cells. However, little is known about the functional role of L1CAM on endothelial cells. We observed that L1CAM expression was selectively enhanced on endothelium associated with pancreatic adenocarcinoma in situ and on cultured pancreatic tumor-derived endothelial cells in vitro. L1CAM expression of endothelial cells could be augmented by incubation with immunomodulatory cytokines such as tumor necrosis factor alpha, interferon gamma, or transforming growth factor beta 1. Antibodies to L1CAM and the respective ligand neuropilin-1 blocked tube formation and stromal cell-derived factor 1beta induced transmigration of tumor endothelial cells in vitro. L1CAM expression on tumor-derived-endothelial cells enhanced Panc1 carcinoma cell adhesion to endothelial cell monolayers and transendothelial migration. Our data demonstrate a functional role of L1CAM expression on tumor endothelium that could favor metastasis and angiogenesis during tumor progression.
authors.affiliation: Tumor Immunology Programme, D015, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Issa
authors.forename: Daniel
authors.initials: D
authors.lastname: Nummer
authors.forename: Tobias
authors.initials: T
authors.lastname: Seibel
authors.forename: Susanne Sebens
authors.initials: SS
authors.lastname: Müerköster
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
authors.forename: Friedrich-Hubertus
authors.initials: FH
authors.lastname: Schmitz-Winnenthal
authors.forename: Luis
authors.initials: L
authors.lastname: Galindo
authors.forename: Juergen
authors.initials: J
authors.lastname: Weitz
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D002465:Cell Movement; D016207:Cytokines / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis*; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000912:Antibodies, Neoplasm; D016207:Cytokines; D009363:Neoplasm Proteins; D039842:Neural Cell Adhesion Molecule L1; D039942:Neuropilin-1